Long non-coding RNA CCDC144NL-AS1 sponges miR-143-3p and regulates MAP3K7 by acting as a competing endogenous RNA in gastric cancer

Hao Fan,Linling Lin,Liang Shi,Wangwang Chen,Jian Xiao,Zengliang Li,Peidong Ni,Yugang Ge,Li Yang,Xiang Ma,Zekuan Xu

doi:10.1038/s41419-020-02740-2

Hao Fan, Linling Lin + Show 9 more

Open Access

https://doi.org/10.1038/s41419-020-02740-2

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Abstract

Gastric cancer (GC) has been one of the most leading cause of cancer-death worldwide. Long non-coding RNAs (lncRNAs) have been found to be related with the carcinogenesis and the development of various cancers, including GC. However, there are still many GC-related lncRNAs functional roles and molecular mechanisms that have not yet been clearly studied. Herein, we report lncRNA CCDC144NL-AS1, which has not been explored in GC, and it is markedly upregulated in GC tissues, which may serve as an independent predictor of poor prognosis. We found that CCDC144NL-AS1 expression was significantly positively associated with a larger tumor size and more pronounced lymph node metastasis. Through a series of in vivo and in vitro functional experiments, we observed that CCDC144NL-AS1 could facilitate cell proliferation, invasion and migration and inhibit cell apoptosis in GC. Further mechanism investigation revealed that CCDC144NL-AS1 acted as a competing endogenous RNA (ceRNA) for sponging miR-143-3p and upregulated the expression of its direct endogenous target MAP3K7 in GC. Taken together, our results elucidate the oncogenic roles of CCDC144NL-AS1/miR-143-3p/MAP3K7 axis in GC progression, providing inspiration for further understanding of the mechanism of GC and making CCDC144NL-AS1 as a potential novel diagnostic and therapeutic target for GC.

Highlights

Gastric cancer (GC) ranks among the highest malignancies, and it is an important risk factor that endangers human health worldwide
By analyzing TCGA STAD database including RNA sequencing (RNA-seq) data of 375 GC tissues and 32 adjacent non-tumor tissues, CCDC144NL-AS1 was identified as GC-associated Long non-coding RNAs (lncRNAs) that may be related with gastric tumorigenesis
The clinicopathologic features of the GC patients showed that high CCDC144NL-AS1 expression was obviously related with a larger tumor size and more profound lymphatic metastasis rate (Table S1).Further, the online Kaplan–Meier plot indicated that a high CCDC144NL-AS1 expression level was correlated with poor overall survival (Fig. 1f)

Summary

Introduction

Gastric cancer (GC) ranks among the highest malignancies, and it is an important risk factor that endangers human health worldwide. Consortium has revealed that the majority of the human genome are transcribed into non-coding RNAs (ncRNAs), while protein-coding genes account for only 2%6. Long non-coding RNAs (lncRNAs) share limited or no proteincoding capacity and have transcripts of more than 200 nucleotides in length[7]. LncRNAs usually play their biological functions by directly or indirectly regulating the expression of potential target genes at epigenetic modification, transcriptional and post-transcriptional levels[8,9]. These biological processes include cell proliferation, Official journal of the Cell Death Differentiation Association

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